Vasopressin signaling pathways in vascular smooth muscle.
Arginine vasopressin (AVP) exhibits both acute and long-term effects on vascular smooth muscle cells (VSMC). Acutely, AVP regulates vascular tone and stimulates contraction. Longer term exposure of VSMC to AVP in the absence of other mitogenic agents results in cell hypertrophy without increases in cell number, and increased expression of a number of muscle-specific genes including the smooth muscle form of alpha-actin (SM-alpha-actin). These responses can be distinguished from the proliferative responses seen with growth factors such as platelet-derived growth factor (PDGF), which increase DNA synthesis and cell number and suppress SM-alpha-actin expression. In cultured VSMC, all the effects of AVP are mediated through the V1a receptor which signals through G-proteins. This review examines post-receptor signaling events mediated by AVP in VSMC. AVP rapidly increases intracellular Ca2+ via mobilization of intracellular stores and entry of extracellular Ca2+ via specific cation channels. This pathway, via activation of myosin light chain kinase, is critical for the early contractile response. Increased intracellular Ca2+ also leads to increased arachidonic acid release and eicosanoid production through the action of phospholipase A2. The activation of protein kinases by AVP is examined, focusing on members of the mitogen-activated protein kinase family. These enzymes are likely to play an important role in promoting growth of VSMC as well as modulating their state of differentiation through transcriptional control of muscle-specific gene expression. Recent studies suggesting a role for c-Jun amino terminal kinases in the regulation of smooth muscle-alpha-actin expression are described.
Nemenoff
R A
RA
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Raphael.Nemenoff@UCHSC.edu
D000199:Actins / Q000235:genetics; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D014667:Vasopressins / Q000494:pharmacology / Q000502:physiology*
D000199:Actins; D015777:Eicosanoids; D014667:Vasopressins; D016718:Arachidonic Acid; D011494:Protein Kinases; D002118:Calcium